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| == Function == | | == Function == |
| [https://www.uniprot.org/uniprot/Q2IU02_RHOP2 Q2IU02_RHOP2] | | [https://www.uniprot.org/uniprot/Q2IU02_RHOP2 Q2IU02_RHOP2] |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Given prominent physicochemical similarities between H(2)O(2) and water, we report a new strategy for promoting the peroxygenase activity of P450 enzymes by engineering their water tunnels to facilitate H(2)O(2) access to the heme center buried therein. Specifically, the H(2)O(2)-driven activities of two native NADH-dependent P450 enzymes (CYP199A4 and CYP153A(M.aq)) increase significantly (by >183-fold and >15-fold, respectively). Additionally, the amount of H(2)O(2) required for an artificial P450 peroxygenase facilitated by a dual-functional small molecule to obtain the desired product is reduced by 95%-97.5% (with approximately 95% coupling efficiency). Structural analysis suggests that mutating the residue at the bottleneck of the water tunnel may open a second pathway for H(2)O(2) to flow to the heme center (in addition to the natural substrate tunnel). This study highlights a promising, generalizable strategy whereby P450 monooxygenases can be modified to adopt peroxygenase activity through H(2)O(2) tunnel engineering, thus broadening the application scope of P450s in synthetic chemistry and synthetic biology.
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| Enabling Peroxygenase Activity in Cytochrome P450 Monooxygenases by Engineering Hydrogen Peroxide Tunnels.,Zhao P, Kong F, Jiang Y, Qin X, Tian X, Cong Z J Am Chem Soc. 2023 Mar 8;145(9):5506-5511. doi: 10.1021/jacs.3c00195. Epub 2023 , Feb 15. PMID:36790023<ref>PMID:36790023</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 8hgc" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
